Inhibition of shock-induced foot tapping behaviour in the gerbil by a tachykinin NK 1 receptor antagonist

Inhibition of shock-induced foot tapping behaviour in the gerbil by a tachykinin NK 1 receptor... The selective tachykinin NK 1 receptor antagonist, 2-( R )-(1-( R )-3,5-Bis(trifluoromethyl)phenylethoxy)-3-( S )-(4-fluoro)phenyl-4-(3-oxo-1,2,4-triazol-5-yl)methylmorpholine (MK-869), has been recently described as a novel therapeutic approach for anxiety/depression. A frequently used model to establish the central nervous system (CNS) activity of tachykinin NK 1 receptor antagonists is the inhibition of NK 1 agonist-induced foot tapping in gerbils. In the present study, we demonstrate that foot tapping can also be induced in most, but not all, gerbils by footshock and associated cues. MK-869 (0.3–3 mg/kg, i.p.) dose-dependently blocked this foot tapping response. This effect was further shown to be due to selective NK 1 receptor blockade, since (2 S ,3 S )- cis -3(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994; 3 mg/kg, i.p.) inhibited foot tapping, whereas its less active enantiomer (2 R ,3 R )- cis -3(2-methoxybenzylamino)-2-phenylpiperidine (CP-100,263; 3 mg/kg, i.p.) had no effect. Diazepam (1–10 mg/kg, i.p.) also inhibited foot tapping, whereas fluoxetine (10–30 mg/kg, i.p.) markedly increased this behaviour. The present data support the view that foot tapping in the gerbil is a behavioural response to an aversive stimulus, and is robustly inhibited by two NK 1 receptor antagonists. The data support a role for tachykinin NK 1 receptor antagonists as novel anxiolytic/antidepressants. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Pharmacology Elsevier

Inhibition of shock-induced foot tapping behaviour in the gerbil by a tachykinin NK 1 receptor antagonist

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Publisher
Elsevier
Copyright
Copyright © 2001 Elsevier Science B.V.
ISSN
0014-2999
DOI
10.1016/S0014-2999(01)00724-5
Publisher site
See Article on Publisher Site

Abstract

The selective tachykinin NK 1 receptor antagonist, 2-( R )-(1-( R )-3,5-Bis(trifluoromethyl)phenylethoxy)-3-( S )-(4-fluoro)phenyl-4-(3-oxo-1,2,4-triazol-5-yl)methylmorpholine (MK-869), has been recently described as a novel therapeutic approach for anxiety/depression. A frequently used model to establish the central nervous system (CNS) activity of tachykinin NK 1 receptor antagonists is the inhibition of NK 1 agonist-induced foot tapping in gerbils. In the present study, we demonstrate that foot tapping can also be induced in most, but not all, gerbils by footshock and associated cues. MK-869 (0.3–3 mg/kg, i.p.) dose-dependently blocked this foot tapping response. This effect was further shown to be due to selective NK 1 receptor blockade, since (2 S ,3 S )- cis -3(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994; 3 mg/kg, i.p.) inhibited foot tapping, whereas its less active enantiomer (2 R ,3 R )- cis -3(2-methoxybenzylamino)-2-phenylpiperidine (CP-100,263; 3 mg/kg, i.p.) had no effect. Diazepam (1–10 mg/kg, i.p.) also inhibited foot tapping, whereas fluoxetine (10–30 mg/kg, i.p.) markedly increased this behaviour. The present data support the view that foot tapping in the gerbil is a behavioural response to an aversive stimulus, and is robustly inhibited by two NK 1 receptor antagonists. The data support a role for tachykinin NK 1 receptor antagonists as novel anxiolytic/antidepressants.

Journal

European Journal of PharmacologyElsevier

Published: Feb 2, 2001

References

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